Scientists uncover another clue to how and where memory is formed

Understanding how and where memories are normally stored in the brain will be the key to developing new treatments for memory disorders. Memories are thought to be created through the strengthening of connections between brain cells (neurons) to form a memory. In a new study led by The Hospital for Sick Children (SickKids), researchers have discovered one important factor that determines which precise neurons are selected to store a given memory and where this memory is stored. The study is published in the August 6 online edition of Neuron.

While the human brain contains over 100 billion neurons, evidence suggests that each memory is supported by a small unique subset of neurons. Scientists have long wondered how is it that one neuron is selected over another to participate in a particular memory trace.

“Our study shows that neurons compete against one another for recruitment to a memory. Winning cells which become part of the memory are those that are more active, or excitable, immediately before a to-be remembered event,” Dr. Sheena Josselyn, Senior Scientist in Neurosciences & Mental Health at SickKids and Associate Professor in the Departments of Psychology and Physiology at the University of Toronto.

The research team used several different techniques to manipulate excitability in a handful of cells in the rodent brain and found that cells that were more active were indeed more likely to wire together and become part of the neural network storing that memory.

“This idea that cell excitability is an important factor in memory formation harkens back to the pioneering work of Canadian psychologist Donald O. Hebb. Hebb’s influential ideas on how memories are formed in the brain lead to the notion that ‘neurons that fire together wire together’,” notes Dr. Paul Frankland, Senior Scientist in Neurosciences & Mental Health at SickKids and Associate Professor in the Departments of Psychology and Physiology.

As a way of examining memory, researchers used Pavlovian conditioning to train rodents to associate a tone with an aversive stimulus. When presented the tone again in a new setting, these rodents exhibited responses showing that they had learned and remembered this association. Intriguingly the study also demonstrates that artificially activating these excitable cells alone was sufficient to induce retrieval of that memory; meaning rodents reacted when these cells were artificially activated as if the tone had been replayed. Therefore, artificial activation of these cells alone caused rodents to recall the memory.

Josselyn explains that this finding is reminiscent of similar early reports by Canadian neurosurgeon Wilder Penfield, who in the 1940s stimulated the brains of humans undergoing surgery for epilepsy which sometimes caused these human patients to recall past events.

Over 30 million North Americans suffer from some type of clinically recognized learning or memory disorder. “From the gradual weakening of memory with age to the ravages of Alzheimer’s disease, memory impairments are also a hallmark of major mental illnesses such as schizophrenia and depression. In order to develop new treatment or prevention strategies, the mechanisms underlying normal memory formation must be understood,” adds Josselyn.

This work was supported by grants from the Canadian Institutes of Health Research (CIHR), Brain and Behavior Foundation (NARSAD), EJLB Foundation and the Alzheimer’s Society of Canada , grants from Natural Sciences and Engineering Research Council of Canada (NSERC), Restracomp Fellowships, a Banting Postdoctoral Fellowship (CIHR) and SickKids Foundation.